4-(3-hydroxyphenyl)pentan-2-one O-(2,4-dinitrophenyl)oxime | 191614-96-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(3-hydroxyphenyl)pentan-2-one O-(2,4-dinitrophenyl)oxime
• 英文别名: 4-(3-hydroxyphenyl)pentan-2-one O-2,4-dinitrophenyloxime；3-[4-(2,4-dinitrophenoxy)iminopentan-2-yl]phenol
• CAS: 191614-96-7
• 化学式: C₁₇H₁₇N₃O₆
• 分子量: 359.338
• InChiKey: AMODQBFAQIHNNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.16
• 重原子数：
  26.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  128.1
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  4-(3-hydroxyphenyl)pentan-2-one O-(2,4-dinitrophenyl)oxime 在 sodium hydride 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 2-[2,4-dichloro-3-(2,4-dimethylquinolin-8-yloxymethyl)benzenesulfonylamino]-2-methylpropionic acid tert-butyl ester
  参考文献：
  名称：

  Design and Synthesis of Novel Sulfonamide-Containing Bradykinin hB₂ Receptor Antagonists. 1. Synthesis and SAR of α,α-Dimethylglycine Sulfonamides

  摘要：

  We recently published the extensive in vivo pharmacological characterization of MEN 16132 (J. Pharmacol. Exp. Ther. 2005, 616- 623; Eur. J. Pharmacol. 2005, 528, 7), a member of the sulfonamide-containing human B-2 receptor (hB(2)R) antagonists. Here we report, in detail, how this family of compounds was designed, synthesized, and optimized to provide a group of products with subnanomolar affinity for the hB2R and high in vivo potency after topical administration to the respiratory tract. The series was designed on the basis of indications from the X-ray structures of the key structural motifs A and B present in known antagonists and is characterized by the presence of an alpha,alpha-dialkyl amino acid. The first lead ( 17) of the series was submitted to extensive chemical work to elucidate the structural requirements to increase hB(2) receptor affinity and antagonist potency in bioassays expressing the human B2 receptor ( hB2R). The following structural features were selected: a 2,4-dimethylquinoline moiety and a piperazine linker acylated with a basic amino acid. The representative lead compound 68 inhibited the specific binding of [H-3] BK to hB(2)R with a pKi of 9.4 and antagonized the BK-induced inositolphosphate (IP) accumulation in recombinant cell systems expressing the hB(2)R with a pA(2) of 9.1. Moreover, compound 68 when administered (300 nmol/kg) intratracheally in the anesthetized guinea pig, was able to significantly inhibit BK-induced bronchoconstriction for up to 120 min after its administration, while having a lower and shorter lasting effect on hypotension.

  DOI：

  10.1021/jm060137l
• 作为产物：
  描述：

  (E)-4-(3-hydroxyphenyl)but-3-en-2-one 在 盐酸 、 copper(l) chloride 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 为溶剂， 反应 2.0h， 生成 4-(3-hydroxyphenyl)pentan-2-one O-(2,4-dinitrophenyl)oxime
  参考文献：
  名称：

  Design and Synthesis of Novel Sulfonamide-Containing Bradykinin hB₂ Receptor Antagonists. 1. Synthesis and SAR of α,α-Dimethylglycine Sulfonamides

  摘要：

  We recently published the extensive in vivo pharmacological characterization of MEN 16132 (J. Pharmacol. Exp. Ther. 2005, 616- 623; Eur. J. Pharmacol. 2005, 528, 7), a member of the sulfonamide-containing human B-2 receptor (hB(2)R) antagonists. Here we report, in detail, how this family of compounds was designed, synthesized, and optimized to provide a group of products with subnanomolar affinity for the hB2R and high in vivo potency after topical administration to the respiratory tract. The series was designed on the basis of indications from the X-ray structures of the key structural motifs A and B present in known antagonists and is characterized by the presence of an alpha,alpha-dialkyl amino acid. The first lead ( 17) of the series was submitted to extensive chemical work to elucidate the structural requirements to increase hB(2) receptor affinity and antagonist potency in bioassays expressing the human B2 receptor ( hB2R). The following structural features were selected: a 2,4-dimethylquinoline moiety and a piperazine linker acylated with a basic amino acid. The representative lead compound 68 inhibited the specific binding of [H-3] BK to hB(2)R with a pKi of 9.4 and antagonized the BK-induced inositolphosphate (IP) accumulation in recombinant cell systems expressing the hB(2)R with a pA(2) of 9.1. Moreover, compound 68 when administered (300 nmol/kg) intratracheally in the anesthetized guinea pig, was able to significantly inhibit BK-induced bronchoconstriction for up to 120 min after its administration, while having a lower and shorter lasting effect on hypotension.

  DOI：

  10.1021/jm060137l

文献信息

• Synthesis of 8-Hydroxyquinolines by the Cyclization of<i>m</i>-Hydroxyphenethyl Ketone<i>O</i>-2,4-Dinitrophenyloximes
  作者：Katsuya Uchiyama、Yujiro Hayashi、Koichi Narasaka

  DOI：10.1055/s-1997-6146

  日期：1997.6

  8-Hydroxyquinolines are synthesized from O-2,4-dinitrophenyloximes of m-hydroxyphenethyl ketones by the treatment with sodium hydride, and then with 2,3-dichloro-4,5-dicyano-p-benzoquinone (DDQ).

  8-羟基喹啉是通过将m-羟基苯乙酮的O-2,4-二硝基苯肟与氢化钠处理，然后再与2,3-二氯-4,5-二氰基对苯醌（DDQ）反应合成的。
• Regioselective Synthesis of Quinolin-8-ols and 1,2,3,4-Tetrahydroquinolin-8-ols by the Cyclization of 2-(3-Hydroxyphenyl)ethyl Ketone<i>O</i>-2,4-Dinitrophenyloximes
  作者：Katsuya Uchiyama、Ayako Ono、Yujiro Hayashi、Koichi Narasaka

  DOI：10.1246/bcsj.71.2945

  日期：1998.12

  Cyclization of 2-(3-hydroxyphenyl)ethyl ketone O-2,4-dinitrophenyloximes proceeds on the oxime nitrogen atom by the treatment with NaH and then with 2,3-dichloro-5,6-dicyano-p-benzoquinone and acetic acid to yield quinolin-8-ols regioselectively. The reaction in the presence of Na[BH3(CN)] affords 1,2,3,4-tetrahydroquinolin-8-ols. The present cyclization proceeds via alkylideneaminyl radical intermediates

  2-(3-羟基苯基)乙基酮 O-2,4-二硝基苯基肟的环化反应在肟氮原子上进行，先用 NaH 处理，然后用 2,3-二氯-5,6-二氰基-对苯醌和乙酸处理区域选择性地产生喹啉-8-醇。在 Na[BH3(CN)] 存在下反应得到 1,2,3,4-四氢喹啉-8-醇。本环化通过亚烷基亚胺基自由基中间体进行，该中间体由 3-羟基苯基和 2,4-二硝基苯基部分之间的单电子转移产生。